The basic objective of this research is to improve the radiotherapy of brain tumors. We have recently demonstrated in split dose experiments that one of the post-irradiation DNA repair mechanisms in cultured cells may be sensitive to a second dose of radiation. If tis were true in vivo and if the DNA repair kinetics of normal nondividing brain cells and brain tumor cells were different, it would be possible to design radiotherapy schedules which can maximize the accumulation of DNA damage in brain tumor while minimizing the DNA damage accumulated in normal brain. Alkaline sucrose gradient ultracentrifugation techniques in zonal rotors (which yield large DNA molecules (greater than 350S) will be used to determine the in situ DNA damage and repair kinetics of both 9L tumor and normal brain cells in Fischer 344 rats. The research objectives are: 1) to determine in situ the DNA damage and repair kinetics of the intercerebral rat 9L brain tumor and normal brain cells after single and split doses of ionizing radiation and, 2) to correlate the accumulation of structural DNA damage with the loss of cellular clonogenic or functional capacity. Because the work will be done in vivo where all the perturbations imposed by the in toto physiological response of the animals to the treatment schedule are included, the final results should be directly relevant to the problems encountered in the clinical management of brain tumors.